Triethylamine → 4-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl ester

HRID 729369노트

반응식

HRID 729369 반응식
[CH2:1]([O:3][C:4](=[O:15])[C:5]1[C:10]([F:11])=[CH:9][C:8](F)=[C:7]([F:13])[C:6]=1[F:14])[CH3:2].C(N(CC)CC)C.[C:23]([O:27][C:28](=[O:35])[NH:29][C@H:30]1[CH2:34][CH2:33][NH:32][CH2:31]1)([CH3:26])([CH3:25])[CH3:24]>C(#N)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]1[C:10]([F:11])=[CH:9][C:8]([N:32]2[CH2:33][CH2:34][C@H:30]([NH:29][C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:35])[CH2:31]2)=[C:7]([F:13])[C:6]=1[F:14])[CH3:2]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 1514396(3S)-(-)-3-(tert-Butoxycarbonylamino)pyrrolidineHCID 210411752,3,4,6-Tetrafluorobenzoic acid ethyl ester

생성물 1

HCID 586818974-[(S)-3-tert-Butoxycarbonylaminopyrrolidin-1-yl]-2,3,6-trifluorobenzoic acid ethyl ester수율 69.8%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A solution of 2,3,4,6-tetrafluorobenzoic acid ethyl ester (Example 1b, 5.1 g, 22.9 mmol), triethylamine (22 mL, 157 mmol), and (S)-pyrrolidin-3-ylcarbamic acid tert-butyl ester (5.2 g, 27.9 mmol) in acetonitrile (60 mL) is stirred at room temperature for 64 hours. The mixture is concentrated in vacuo and the residue dissolved in chloroform, washed with NaHCO3 and then brine, dried over Na2SO4, filtered, and concentrated under vacuum to afford a solid. The solid is purified by column chromatography (1:1:7 ethyl acetate/chloroform/hexanes) to afford the title compound (6.21 g). 1H NMR (CDCl3): δ 6.07 (ddd, 1H), 4.78-4.63 (bd, 1H), 4.49-4.22 (m, 3H), 3.80-3.68 (m, 1H), 3.66-3.28 (m, 3H), 2.33-2.13 (m, 1H), 2.04-1.83 (m, 1H), 1.45 (s, 9H), 1.36 (t, 3H).

후처리

  1. concentrationThe mixture is concentrated in vacuo
  2. dissolutionthe residue dissolved in chloroform
  3. washwashed with NaHCO3
  4. dry with materialbrine, dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customto afford a solid
  8. customThe solid is purified by column chromatography (1:1:7 ethyl acetate/chloroform/hexanes)

출처 및 근거

ORD 기록
ord-365db204377245cea45f9f4e07e23c62
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582627B2

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